The ability to generate cytotoxic T lymphocyte responses to minor H antigens offers a potent tool for the study of self-tolerance and self-recognition. Results obtained in this system have thus far demonstrated 1) that the self + X T cell repetoire is highly cross-reactive for allogeneic MHC determinents suggesting that the response to allogenic MHC antigens is comprised of multiple self + X specificities and 2) that self minor H determinents tolerize T cells only in association with self MHC determinents so that tolenance induction to non MHC self components is restricted by MHC encoded products. Thus, these results demonstrate that the induction of T cell tolerance to self components is genetically restricted by MHC gene products.